For the fetus, although the roles of arterial blood gases are recognized to be critical in the regulation of cerebral blood flow (CBF) and cerebral oxygenation, the relation of CBF, cortical tissue P(O2) (tP(O2)), sagittal sinus P(O2), and related indices of cerebral oxygenation to arterial blood gases are not well defined. This is particularly true for that fetus subjected to long-term hypoxia (LTH). In an effort to elucidate these interrelations, we tested the hypothesis that in the fetus acclimatized to high altitude, cerebral oxygenation is not compromised relative to that at low altitude. By use of a laser Doppler flowmeter with a fluorescent O2 probe, in near-term fetal sheep at low altitude (n = 8) and those acclimatized to high altitude hypoxia (3801 m for 90 +/- 5 days; n = 6), we measured laser Doppler CBF (LD-CBF), tP(O2), and related variables in response to 40 min superimposed hypoxia. At both altitudes, fetal LD-CBF, cerebral O2 delivery, tP(O2), and several other variables including sagittal sinus P(O2), correlated highly with arterial P(O2) (P(a,O2)). In response to superimposed hypoxia (P(a,O2) = 11 +/- 1 Torr), LD-CBF was significantly blunted at high altitude, as compared with that at low altitude. In the two altitude groups fetal cerebral oxygenation was similar under both control conditions and with superimposed hypoxia, cortical tP(O2) decreasing from 8 +/- 1 and 6 +/- 1 Torr, respectively, to 2 +/- 1 Torr. Also, for these conditions sagittal sinus P(O2) and [HbO2] values were similar. In response to superimposed hypoxia, cerebral metabolic rate for O(2) decreased approximately 50% in each group (P < 0.05). For both the fetus at low altitude and that acclimatized to high altitude LTH, we present the first dose-response data on the relation of LD-CBF, cortical tP(O2), and sagittal sinus blood gas values to P(a,O2). In addition, despite differences in several variables, the fetus at high altitude showed evidence of successful acclimatization, supporting the hypothesis that such fetuses demonstrate no compromise in cerebral oxygenation.